As a hard-core biochemist, I see the process of genetic inheritance through molecular eyes and, specifically, through the prism of transcription. My scientific journey has taken a path through evolution that began with trying to understand how genes got turned on (and off) in bacteria while I was a graduate student in the Harvard University laboratory of Richard Losick, now an HHMI professor. As a postdoc in Jim Watson's lab at the Cold Spring Harbor Laboratory, I studied a monkey virus called SV40 that does its damage by taking control of the genetic machinery of an infected primate cell. These early studies provided a path for discovering the huge family of regulatory proteins called transcription factors that govern how a gene gets activated. Thousands of such factors have now been found, along with a host of related molecules—all required to control gene activity.

Today, my lab group is trying to pin down the extraordinarily elastic orchestration of gene regulation in stem cells: What mechanisms allow the flexible capacity of genetic programs that define stem cells? What regulates the expression of genes specific to a particular cell type, such as muscle, liver, or neuron? Pushed by a highly creative group of graduate students and postdocs, we are finding surprising answers. We have also learned a major lesson: The machinery that has evolved is more elaborate, diversified, and convoluted than anyone anticipated. And that is a continuing source of wonder.

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